Although the pathophysiologic response of the brain to a reduced oxygen availability has been studied for many years the exact mechanism by which cerebral damage is incurred is not known. It is also unclear whether the mechanism of damage is the same for ischemia (a reduction in cerebral blood flow) and hypoxia (a reduction in blood oxygen content). The overall goals of this project are to clarify the role of oxygen derived free radical mechanisms in the pathophysiology of global cerebral ischemia and hypoxia and to determine if the apparent ability of newborn animals to tolerate reduced cerebral oxygen availability is related to a free radical mechanism. We hypothesize that increasing the duration of an ischemic insult is associated with decreased recovery of post ischemic cerebral blood flow and oxygen consumption, decreased post ischemic recovery of neurologic function and increased post ischemic production of oxygen derived free radicals, but that these changes will be less marked in newborns. Likewise, we hypothesize that there will be an increased release of oxygen derived free radicals during reoxygenation after pure hypoxia. Ischemia will be induced by cross clamping the ascending aorta after occlusion of the vena cavae. In both newborn and older animals ischemia will be maintained for variable times to determine whether changing the interval of ischemia or the administration of oxygen derived free radical scavengers (e.g. superoxide dismutase) has an effect on post ischemic sequela. The variables that will be measured include cerebral blood flow (radiolabelled microsphere technique), cerebral oxygen consumption (Fick principle), cerebral function (evoked potentials) and production of oxygen derived free radicals (nitroblue-tetrazolium technique). Cerebral hypoxia will be produced by lowering the inspired oxygen content while maintaining arterial PCO2 and pH normal. In this group of animals hypoxia will be maintained at one of two levels (5% or 10% O2) for ten minutes and the rate of free radical production will be determined during reoxygenation. From our data we will be able to determine whether oxygen derived free radical mechanisms are associated with cerebral ischemia or hypoxia.